Project Summary/Abstract Sensorineural hearing loss (SNHL) is a source of significant morbidity and in isolated cases is irreversible. Most cases of SNHL are associated with damage or loss of cochlear hair cells. The diagnosis of SNHL is based primarily on audiometric testing as the inner ear cannot be ?biopsied? without causing profound hearing loss. Contemporary imaging techniques (computed tomography (CT) and magnetic resonance imaging (MRI)) provide a macroscopic glimpse of peripheral and central auditory pathways but cannot resolve detailed anatomy of the inner ear, at the cellular level. The rapidly growing field of hair cell regeneration is poised to transform our ability to improve SNHL using small molecule or gene therapy approaches but is hampered by the inability to directly image hair cell pathology. Physical Sciences Inc. (PSI), in collaboration with the Eaton Peabody Laboratories at the Massachusetts Eye and Ear Infirmary (MEEI) proposes to develop a multimodal endoscopic imaging system that combines optical coherence tomography (OCT) and auto-fluorescence imaging (AFI) to simultaneously acquire anatomical and biochemical changes of the cochlea, which can be used to diagnose SNHL. During a Phase I program, PSI has developed a bench-top OCT/AFI instrument and has demonstrated the feasibility of this approach to reliably visualize intracochlear anatomy and biochemical functionality in a mouse animal model of SNHL. In a Phase II program we propose to develop an endoscopic OCT/AFI instrument with improved performance, suitable for in vivo use in a large animal model of SNHL. If successful, this technology will be a major step forward in our ability to diagnose SNHL and guide future targeted therapies for inner ear regeneration. Furthermore, this technology will be invaluable in surgical planning during hearing preservation approaches for cochlear implantation.